Natural Product: NPC31509

Natural Product IDNPC31509
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RMVNOXTYYNGKFC-LURJTMIESA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 97053228
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0000060] Alpha amino acids and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey RMVNOXTYYNGKFC-LURJTMIESA-N
Standard InCHI InChI=1S/C8H10N2O2/c11-8(12)6-2-1-3-7-9-4-5-10(6)7/h4-6H,1-3H2,(H,11,12)/t6-/m0/s1
SMILES C1C[C@@H](C(=O)O)n2ccnc2C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   166.07 Volume:   161.476
?
Van der Waals volume.
Dense:   1.028 LogP:   -0.976
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.109
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.831
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   11.0
TPSA:   55.12
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.672 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.094 Fsp3:   0.5
MCE-18:   36.667
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.014 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.034
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.094
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.016 Promiscuous compounds:   0.587

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.641 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.0 Pgp-substrate:   0.194
PAMPA:   0.977
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.005
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.008
50% Bioavailability (F50%):   0.009

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.175 MRP1:   0.908
Plasma Protein Binding (PPB):   14.158% Volume Distribution (VD):   -0.517
Fu: 82.641%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.037
OATP1B3 inhibitor:   0.038 BCRP inhibitor:   0.012
BSEP inhibitor:   0.097

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.774 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.054 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.0
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  2.179 Half-life (T1/2):  2.158

ADMET: Toxicity

hERG Blockers:  0.098 hERG Blockers (10um):  0.065
Human Hepatotoxicity (H-HT):  0.724 Drug-induced Liver Injury (DILI):  0.96
AMES Toxicity:  0.312 Rat Oral Acute Toxicity:  0.372
Maximum Recommended Daily Dose:  0.583 Skin Sensitization:  0.936
Carcinogencity:  0.426 Eye Corrosion:  0.027
Eye Irritation:  0.546 Respiratory Toxicity:  0.74
Drug-induced Neurotoxicity:  0.83 Ototoxicity:  0.709
Hematotoxicity:  0.168 Drug-induced Nephrotoxicity:  0.905
Genotoxicity:  0.965 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.011 Hek293 Cytotoxicity:  0.023
BCF:   0.162
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   2.781
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.068
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.276
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. root n.a. PMID[10364842]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. root n.a. PMID[12392098]
NPO16914 Abacopteris penangiana n.a. n.a. n.a. Rhizomes n.a. n.a. PMID[16499328]
NPO16914 Abacopteris penangiana n.a. n.a. n.a. n.a. rhizome n.a. PMID[16499328]
NPO16914 Abacopteris penangiana n.a. n.a. n.a. aerial parts Jiangxi Province, China 2004-JUN PMID[17922550]
NPO21717 Acremonium chrysogenum Species n.a. Eukaryota n.a. n.a. n.a. PMID[23089729]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[24996657]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. root n.a. PMID[25767328]
NPO1816 Pterogorgia citrina Species Gorgoniidae Eukaryota n.a. Caribbean n.a. PMID[7911157]
NPO14792 Abies grandis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17598 Maytenus mossambicensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22249 Senecio leptolobus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16914 Abacopteris penangiana n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO12178 Pinellia pedatisecta Species Araceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1816 Pterogorgia citrina Species Gorgoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12178 Pinellia pedatisecta Species Araceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12178 Pinellia pedatisecta Species Araceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17598 Maytenus mossambicensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12178 Pinellia pedatisecta Species Araceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16559 Darwinia grandiflora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12400 Cereus gummosus Species Sagartiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21717 Acremonium chrysogenum Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17137 Nymania capensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1816 Pterogorgia citrina Species Gorgoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22249 Senecio leptolobus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3210 Polyporus arcularius Species Polyporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21752.1 Bauhinia forficata subsp. pruinosa Subspecies Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16689 Corydalis clavicula Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15728 Prunus nipponica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17598 Maytenus mossambicensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO309 Phyla canescens Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12178 Pinellia pedatisecta Species Araceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14792 Abies grandis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO814 Acipenser sturio Species Acipenseridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16914 Abacopteris penangiana n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO16208 Viguiera pinnatiloba Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17755 Inula helenium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10736 Teucrium kotschyanum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC31509 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
NPC

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC31509 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data